Biologically effective dose (BED) for interstitial seed implants containing a mixture of radionuclides with different half-lives.

PURPOSE: To develop a tool for evaluating interstitial seed implants that contain a mixture of radionuclides with different half-lives and to demonstrate its utility by examining the clinical implications of prescribing to an isodose surface for such an implant. METHODS AND MATERIALS: A linear-quadratic model for continuous low dose rate irradiation was developed for permanent implants containing a mixture of radionuclides. Using a generalized equation for the biologically effective dose (BED), the effects of cell proliferation and sublethal damage repair were examined systematically for implants containing a mixture of radionuclides. A head-and-neck permanent seed implant that contained a mixture of (125)I and (103)Pd seeds was used to demonstrate the utility of the generalized BED.
RESULTS: An equation of BED for implants containing a mixture of radionuclides with different half-lives was obtained. In such an implant, the effective cell kill was shown to depend strongly on the relative dose contributions from each radionuclide type; dose delivered by radionuclides with shorter half-life always resulted in more cell kill for any given sublethal damage repair and cell proliferation rates. Application of the BED formula to an implant containing a mixture of (125)I and (103)Pd seeds demonstrates that the conventional dose prescription to an isodose surface is not unique for such an implant. When the prescription dose was based on existing clinical experience of using (125)I seeds alone, mixing (103)Pd seeds with (125)I seeds would increase the cell kill. On the other hand, if the prescription dose were based on existing clinical experience of using (103)Pd seeds alone, mixing (125)I seeds with (103)Pd seeds in the same implant would create radiobiologically "cold" spots (i.e., an increase in cell survival) at locations where a major portion of the prescription dose is contributed by the (125)I seeds. For fast-growing tumors, these "cold" spots can become significant.
CONCLUSIONS: Total dose alone is no longer sufficient for a complete characterization of a permanent seed implant containing a mixture of radionuclides with different half-lives due to the presence of cell proliferation and sublethal damage repair in the protracted dose delivery. BED provides a tool for evaluating the radiobiologic effects of mixing different type of radionuclides in the same implant. When radionuclides of different half-lives are mixed in a permanent implant, using the dose prescription established from existing clinical experience of implants with the longer half-life radionuclide would help to avoid radiobiologic "cold" spots.